In a new study, researchers from the UK and Canada provide more evidence linking a commonly prescribed class of blood pressure medication to an elevated risk in lung cancer. But is the data strong enough to make us reconsider their use?
Angiotensin-converting enzyme inhibitors (ACEIs) are given to millions of people worldwide to treat a variety of vascular conditions, including hypertension (high blood pressure), coronary artery disease, heart failure, diabetes, chronic kidney diseases, and migraines. Highly effective and often free of any noticeable side effects, ACEIs have become a lifeline in the era of rampant heart disease and diabetes.
Several recent studies have confirmed that short-term regimens of ACEIs are safe, but data on the long-term impacts are less clear. Some investigations following ACEI users have found higher than normal rates of multiple types of cancer, whereas others have found no additional risk. These conflicting results have caused debate within the medical community. One group argues that the cancer risk statistics could merely be the result of other health and lifestyle factors, as is known to happen in retrospective studies. The other claims they are valid and point to a handful of biological studies that have revealed ACEIs can cause an accumulation of cancer-associated inflammatory molecules in the lungs.
Hoping to re-evaluate the cancer risk, the researchers examined health record information from the UK Clinical Practice Research Database (CPRD). They selected 992,061 patients who began a new blood pressure medication regimen between 1995 and 2015, following them until the study endpoint in December 2016, or until a diagnosis of cancer or death.
After adjusting their calculations for a number of factors, the team found that, overall, people who took ACEIs had a 14 percent greater risk of lung cancer compared to those who took angiotensin receptor blockers – drugs that have a similar effect on the body but work by a different mechanism.
However, their analysis also showed that people who took ACEIs for less than five years did not have an increased risk. Those with five to 10 years of use had a 22 percent greater risk, and those with ten or more years of consistent use carried a 31 percent elevated risk. The results have been published in the British Medical Journal.
“Although the magnitudes of the observed associations are modest, ACEIs are one of the most widely prescribed drug classes; in the UK, 70.1 million antihypertensives are dispensed each year, of which approximately 32% are ACEIs,” the authors wrote. “Thus, small relative effects could translate into large absolute numbers of patients at risk for lung cancer. Given the potential impact of our findings, they need to be replicated in other settings, particularly among patients exposed for longer durations.”
But making matters more complicated, other medical researchers are claiming that the study may be plagued by the very same correlation-not-causation issues that the authors were trying to minimize. Speaking to the Science Media Centre, Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said:
“[This study] has a number of weaknesses, which make it quite likely that the observed association is not a causal one. This is mainly because of inadequacies in the underlying data, and a possible weakness in the analysis.”
Evans notes that one major limitation stems from the fact that CPRD contains poorly recording smoking data that does not distinguish heavy from light smoking. Heavy smoking is tied to a 20-fold increase in lung cancer risk. Additionally, “ACEIs almost certainly prevent deaths from heart disease and that means that especially after long follow-up, the cohort of ACEI users may contain those at higher risk of lung cancer.”
“Drawing strong conclusions and talking about public health impact in this situation seems premature.”